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微小RNA-34a通过靶向E2F5增强胃癌细胞对紫杉醇治疗的敏感性。

miRNA-34a enhances the sensitivity of gastric cancer cells to treatment with paclitaxel by targeting E2F5.

作者信息

Li Lina, Wu Cuiling, Zhao Yue

机构信息

Department of Pathology, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.

Department of Biochemistry, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.

出版信息

Oncol Lett. 2017 Jun;13(6):4837-4842. doi: 10.3892/ol.2017.6041. Epub 2017 Apr 18.

Abstract

Gastric cancer (GC) is one of the most common types of malignant cancer worldwide, however improvements are required to the current therapies for GC. Although paclitaxel is one of the most promising chemotherapeutic agents in clinical use for GC, the resistance to paclitaxel that develops during treatment is a major obstacle to further treatments of GC. The present study reports that micro (mi) RNA-34a, a tumor suppressor in various types of cancer, may be an important regulator of chemoresistance in GC, as miRNA-34a mimics and inhibitors, enhance and inhibit the chemotherapeutic efficacy of paclitaxel, respectively. In addition, the present study identified that E2F transcription factor 5 (E2F5), a key oncogenic protein, is the direct target candidate of miRNA-34a. Previous studies have demonstrated that the inhibition of E2F5 by specific E2F5 small interfering RNA also increases the sensitivity of GC cells to paclitaxel. In conclusion, the present data suggest that miRNA-34a enhances the treatment of sensitive GC cells to paclitaxel by targeting E2F5. Therefore, the miRNA-34a/E2F5 axis appears to be a potential promising therapeutic target for overcoming the chemotherapeutic resistance of GC.

摘要

胃癌(GC)是全球最常见的恶性肿瘤类型之一,然而目前的GC治疗方法仍需改进。尽管紫杉醇是临床上用于GC最有前景的化疗药物之一,但治疗过程中出现的对紫杉醇的耐药性是GC进一步治疗的主要障碍。本研究报告称,微小(mi)RNA - 34a作为多种癌症中的肿瘤抑制因子,可能是GC化疗耐药的重要调节因子,因为miRNA - 34a模拟物和抑制剂分别增强和抑制了紫杉醇的化疗效果。此外,本研究确定关键致癌蛋白E2F转录因子5(E2F5)是miRNA - 34a的直接靶标候选物。先前的研究表明,用特异性E2F5小干扰RNA抑制E2F5也会增加GC细胞对紫杉醇的敏感性。总之,目前的数据表明,miRNA - 34a通过靶向E2F5增强了敏感GC细胞对紫杉醇的治疗效果。因此,miRNA - 34a/E2F5轴似乎是克服GC化疗耐药性的一个潜在有前景的治疗靶点。

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